My initial goal is to chemically define the relationships among the five components which participate in prothrombin activation. This proposal includes: 1) Determination of the specific action of factor Xa (thrombokinase or autoprothrombin C) in proteolysis of prothrombin; 2) Determination of how phospholipid surfaces increase the rate of thrombin formation and how the lipid surface may localize thrombin formation at a specific site; 3) Determination of the role of divalent cations, usually Ca2 ion, in both lipid-protein interactions and in the proteolytic events of prothrombin activation; and 4) Determination of the chemical action of factor V (accelerator globulin) in prothrombin activation. Factor V and the effect of thrombin on factor V appear to be particularly important in the regulation of prothrombin activation. On the basis of the data obtained from this intensive characterization of prothrombin activation, mechanisms by which thrombin formation may be regulated will be proposed and investigated.